It’s urgent to develop benzocyclobutene (BCB)-based polymers with low curing temperatures for temperature-sensitive applications such as liquid crystal display (LCD) and flexible electronics. Herein, the effect of substituents on the ring-opening behavior of BCB derivatives was investigated. The ring-opening activation energy barriers (ΔGA) of BCB derivatives with one or two substituents on the four-membered alkyl ring were systematically calculated using the B3LYP function. Both mono- and di-substituted BCBs adopted the conrotatory ring-opening process, obeying the Woodward-Hoffmann’s Rules upon heating. The mono-/di-substituted BCBs ex-hibited 8.2 – 69% lower ΔGA compared with BCB, attributed to the electronic effects of the substituents. Disubstituted BCBs with both electron-donating and electron-withdrawing groups, e.g., 1-NH2-8-NO2-BCB, demonstrated the lowest ΔGA. In addition, BCB derivatives with amide/ester/acyloxy group modified on C1 position were synthesized as model molecules, and their ring-opening temperature can be decreased by 20 °C compared to the unsubstituted one, also consistent with our calculation results. This work combined the theoretical calculation method with experimental results to provide valuable insights into the design and synthesis of BCB derivatives and next-generation BCB functional packaging materials with low ring-opening temperatures.
Various optically active polymers are known to afford sophisticated chirality-related functionalities, i.e. asymmetric catalysis, chiroptical switching and memory in UV-vis-NIR region, chromatographic separation of enantiomers, and sensors for molecular chirality. Recently, material researchers are received much attention to design chiral supramolecular architectures from achiral polymers upon intermolecular interactions with help of greener biosources. The present article reports an instantaneous generation of ambidextrous supramolecules revealing light-driven chiroptical switching/memory in UV-vis region when achiral azobenzene-containing vinylpolymers are non-covalently interacted with alkyl ester derivatives of natural cellulose and D-/L-glucose. It was recognized that the semi-synthetic biomaterials efficiently work as chirality-inducing scaffoldings to several achiral and optically inactive molecules, oligomers, and polymers. Our successful results shed light on a new approach of how inexpensive poly-/mono-saccharide derivatives can afford supramolecular chiroptical systems with the azobenzene pendant polymer as aggregates in suspension and liquid-crystalline films with minimal energy, time, and cost.
Structural batteries have emerged as a promising alternative to address the limitations of conventional batteries, with the potential to integrate energy storage into stationary constructions or mobile vehicles/planes. Developing multifunctional composites is effective to realize the structural plus concept, which can reduce the inert weight and improve the performance of the energy storage beyond the material level (e.g., cell- or system-level). Specifically, multifunctional composites in structural batteries can work as both a functional composite electrode to store charges and a structural composite to bear mechanical loads. However, they suffer from the trade-off between mechanical properties and energy storage performance due to the scientific challenges of unstable interfaces and the lack of viable manufacturing approaches. In this review, we first introduce recent research developments of electrodes, electrolytes, separators, and interface engineering specific to structure plus composites for structure batteries, and then summarize the mechanical and electrochemical characterizations. We discuss in detail the reinforced multifunctional composites for structure batteries, the exploration of multifunctionalities on different composite structures and battery configurations, and then conclude with a perspective on future opportunities. The knowledge synthesized in this review contributes to the advancement of this field and facilitates the realization of efficient and durable energy storage systems integrated into structural components.
Apicomplexan parasites comprise significant pathogens of humans, livestock, and wildlife, but also represent a diverse group of eukaryotes with interesting and unique cell biology. Study of cell biology in apicomplexan parasites is complicated by their small size, and historically this has required the application of cutting-edge microscopy techniques to investigate fundamental processes like mitosis or cell division in these organisms. Recently, a technique called expansion microscopy has been developed, which rather than increasing instrument resolution like most imaging modalities, physically expands a biological sample >4-fold. In only a few years since its development, a derivative of expansion microscopy known as ultrastructure-expansion microscopy (U-ExM) has been widely adopted and proven extremely useful for studying cell biology of Apicomplexa. Here we review the insights into apicomplexan cell biology that have been enabled through the use of U-ExM, with a specific focus on Plasmodium, Toxoplasma, and Cryptosporidium. Further, we summarise emerging expansion microscopy modifications and modalities and forecast how these may influence the field of parasite cell biology in future.
Rationale: Trimetazidine and its metabolites are prohibited substances in sports. With a growing number of adverse findings in human athletes, it is crucial to develop doping control strategies that include screening for trimetazidine in animal sports. This study aims to detect and characterize trimetazidine and its metabolites for doping control in camel racing. Methods: Camel urine and plasma samples were collected from four healthy animals following a single oral dose of trimetazidine. invitro studies utilized camel liver cells. Liquid-liquid extraction (LLE) and solid-phase extraction (SPE) techniques were employed for the extraction of trimetazidine metabolites from plasma and urine matrices, the metabolites were analyzed using a thermo Orbitrap exploris LCMS system with optimized settings to achieve maximum sensitivity and accurate mass measurements. Results: Comprehensive metabolite profiling of trimetazidine in camels revealed the identification of seven phase I and five phase II metabolites. Phase I metabolites were primarily formed through delakylation, while phase II metabolites were dominated by glucuronide conjugation of demethylated trimetazidine. The findings provided insights into the distinct metabolic pathways and biotransformation patterns of trimetazidine in camels under the experimental conditions. Conclusion: The developed method enables detection and characterization of trimetazidine and its metabolites in camels. The identified metabolites have the potential to serve as biomarkers for trimetazidine abuse in camel racing .this study provides valuable insights into the metabolism of trimetazidine in camels.
A 59-year-old male was incidentally diagnosed with a left atrial mitral valve chordae involving the junction of the A1 and A2 mitral valve leaflets and resulting in moderate mitral regurgitation. The recognition of this extremely rare congenital malformation prevented over diagnosis and overtreatment.
Gestational diabetes mellitus, pre-eclampsia and future cardiovascular disease: need to consider both BMI and gestational weight gain to investigate the linkLionel Carbillon1, 3, Amélie Benbara1, Emmanuel Cosson2, 31Department of Obstetrics and Gynecology, Paris-Seine Saint Denis University Hospitals, Assistance Publique – Hopitaux de Paris, Paris 13 University, France2 Department of Endocrinology, Diabetology, Nutrition, Paris-Seine Saint Denis University Hospitals, Assistance Publique – Hôpitaux de Paris, France3Sorbonne North Paris University
The number of SARS-CoV-2 recombinants identified during the pandemic has increased since the era of Omicron variants, but XBB.1.5 (or Omicron 23A) is the first lineage comprised of hybrid genomes to predominate at the country and global scales. Very interestingly, the XBB.1.5 recombinant, like the Marseille-4B subvariant (B.1.160/20A.EU2) and the pandemic variant B.1.1.7 (20I/Alpha) previously, has its ORF8 gene inactivated by a stop codon. XBB.1.5 was generated through two successive main events: a recombination between SARS-CoV-2 of lineages BA.184.108.40.206 (BJ.1) and BA.2 220.127.116.11.1 (BM.1.1.1) that generated the XBB (22F) lineage; then ORF8 gene inactivation by a stop codon. We further identified that a stop codon was present at 89 (74%) codons of the ORF8 gene in ≥1 of 15,222,404 genomes available in GISAID, and at 15 codons (12%) in ≥1,000 genomes. Thus, it is very likely that stop codons in ORF8 gene contributed on at least 3 occasions and independently during the SARS-CoV-2 pandemic to the evolutionary success of a lineage that became transiently predominant, most recently XBB.1.5. Such association of gene loss with evolutionary success, which suits the recently described Mistigri rule, is an important biological phenomenon very unknown in virology while largely described in cellular organisms.
Yeast research is entering into a new period of scholarship, with new scientific tools, new questions to ask, and new issues to consider. The politics of emerging and critical technology can no longer be separated from the pursuit of basic science in fields, such as synthetic biology and engineering biology. Given the intensifying race for technological leadership, yeast research is likely to attract significant investment from government, and that it offers huge opportunities to the curious minded from a basic research standpoint. This article provides an overview of new directions in yeast research, and places these trends in their geopolitical context. At the highest level, yeast research is situated within the ongoing convergence of the life sciences with the information sciences. This convergent effect is most strongly pronounced in areas of AI-enabled tools for the life sciences, and the creation of synthetic genomes, minimal genomes, pan-genomes, neochromosomes and metagenomes using computer assisted design tools and methodologies. Synthetic yeast futures encompass basic and applied science questions that will be of intense interest to government and non-government funding sources. It is essential for the yeast research community to map and understand the context of their research in order to ensure their collaborations turn global challenges into research opportunities.
We are evaluating the use of metabolically competent HepaRG™ cells combined with CometChip for DNA damage and the micronucleus (MN) assay as a follow up for in vitro positive genotoxic response as alternatives to in vivo genotoxicity testing.. Naphthalene is genotoxic with rat liver S9 in human TK6 cells inducing a nonlinear dose-response for the induction of micronuclei in the presence of rat liver S9. To follow up this response, we used metabolically competent HepaRG™ cells as a New Approach Methodology (NAM) alternative to animals for genotoxicity assessment of naphthalene. In HepaRG™ cells, naphthalene genotoxicity was assessed using 12 concentrations of naphthalene with the top dose used for assessment of genotoxicity of 1.7 mM corresponding to 45% cell survival. In contrast to human TK6 cell with S9, Naphthalene was not genotoxic in either the HepaRG™ MN Assay or the Comet Assay using CometChip. The lack of genotoxicity in both the MN and comet assays in HepaRG™ cells is likely due to Phase II enzymes removing phenols preventing further bioactivation to quinones and efficient detoxication of naphthalene quinones or epoxides by glutathione conjugation. In contrast to CYP450 mediated metabolism, these Phase II enzymes are inactive in rat liver S9 due to lack of appropriate cofactors causing a positive genotoxic response. This data indicates that rat liver S9-derived BMD10 over-predicts naphthalene genotoxicity BMD calculations when compared to hepatocytes. Metabolically competent hepatocyte models like HepaRG™ cells should be considered as human-relevant NAMs for use genotoxicity assessments to reduce reliance on rodents.
Severe Refractory Hemorrhagic Cystitis after Hematopoietic Cell Transplantation Responds to Recombinant Human Keratinocyte Growth Factor (KGF) - A Case Report and Review of the LiteratureCatherine Hughes1*, Anora Harris1*, Benjamin Watkins1, Muna Qayed1, Suhag Parikh1, Edwin Horwitz1, Elizabeth Stenger1, Kirsten M Williams1, Michelle L Schoettler1
Introduction: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. Methods: Participants aged 6-23 born ≤32 (N=288; 132 with bronchopulmonary dysplasia) and ≥37 weeks’ gestation (N=76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400mcg salbutamol was classified according to published criteria. Results: A BDR was identified in 30.9% (n=85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k=0.26; 95%CI 0.18 to 0.40, p<0.001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs 11%, p=0.010) and baseline resistance (Rrs 5 z-score mean difference (MD)= 0.86, 95%CI 0.07 to 1.65, p=0.025), but similar spirometry to the group without a BDR (FEV 1 z-score MD= -0.01, 95%CI -0.66 to 0.68, p>0.999). Oscillometry was more feasible than spirometry (95% vs 85% (FEV 1), 69% (FVC), p<0.001), however being born preterm did not affect test feasibility. Conclusion: In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to that measured by spirometry and thus these tests should not be used interchangeably.
Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene typically cause severe health complications in multiple organ systems, including the respiratory and gastrointestinal systems. Certain CFTR mutations, however, cause milder clinical phenotypes which may delay confirmatory diagnosis and treatment. Moreover, rare CFTR variants are not studied frequently or approved for genotype specific CFTR modulator therapies, creating further disadvantage. Herein, we describe a personalized medicine approach for a CF patient with three CFTR variants and mild clinical disease to aid in the diagnosis of CF and development of an optimized treatment plan. This strategy relied on the synergistic combination of advanced genetic analyses, patient-derived models of CFTR function and modulation, and personalized clinical care delivery. Whole Exome Sequencing revealed three compound heterozygous CFTR variants: c.2249C>T (p.P750L), c.1408G>A (p.V470M), and c.1251C>A (p.N417K). The CFTR channel function and nature of protein defects for both V470M and N417K mutations are not previously characterized. Patient-derived intestinal organoid models demonstrated residual CFTR channel activity, with improvement in channel function following treatment with the CFTR modulators. / n vitro studies in heterologous model system demonstrated that P750L has the features of Class II CFTR mutations, whereas V470M/N417K exhibited characteristics of Class II, III, and IV mutations, with all three variants responding to the combination modulator therapy of elexacaftor, tezacaftor, and ivacaftor (ETI) and showing functional rescue to near-wild-type CFTR levels. The laboratory data was then utilized to inform patient care, including off-label prescription of ETI. Following 18 months of ETI therapy, significant improvements were noted in key clinical outcomes, including sweat chloride, nutritional parameters, and respiratory and gastrointestinal symptoms. This study demonstrates a personalized medicine approach across clinical and laboratory domains used to care for CF patients with atypical symptoms and/or rare CFTR mutations.
Survival among juvenile ungulates is an important demographic trait affecting population dynamics. In many systems, juvenile ungulates experience mortality from large carnivores, hunter harvest and climate-related factors. These mortality sources often shift in importance both in space and time. While wolves (Canis lupus) predate on moose (Alces alces) throughout all seasons, brown bear (Ursus arctos) predation and human harvest happen primarily during early summer and fall, respectively. Hence, understanding how the mortality of juvenile moose is affected by predation, harvest and climate is crucial to adaptively managing populations and deciding sustainable harvest rates. We used data from 39 female moose in south-central Scandinavia to investigate the mortality of 77 calves in summer/fall and winter/spring, in relation to carnivore presence (defined as wolf presence and bear density), summer productivity, secondary road density, winter severity and migratory strategy (migratory versus resident) using logistic regressions. Summer mortality varied significantly between years but was not correlated to any of our covariates. In winter, calf mortality was higher with deeper snow in areas with wolves compared to areas without and increased more strongly with an increasing proportion of clearcuts/young forests in the presence of wolves compared to when wolves were absent. Lastly, increasing hunting risk was associated with higher calf mortality, and migratory females had higher calf mortality compared to stationary ones. Our study provides useful insight into mortality rates of moose calves coexisting with two large carnivores and with an intensive harvest pressure. Increasing our understanding of the mechanisms driving calf mortality both in summer and winter will become increasingly important if the populations of wolves and bears continue to expand and the moose population declines, and both summers and winters become warmer.
Urban environments represent a theatre for life history evolution. Species able to survive in cities can adapt to the local and often divergent environmental conditions compared to rural or natural environments. Dispersal determines establishment, gene flow, and thus the potential for local adaptation. Since habitats in urban environments are highly fragmented, and showing substantial turnover, contrasting adaptive effects on dispersal are expected. Fragmentation selects against dispersal while patch turn-over is expected to promote the evolution of dispersal. We here show both processes to act in concert when different scales are considered. Dispersal behaviour of juvenile, lab-reared garden spiders from two mid-sized European cities were tested under standardized conditions. While long-distance dispersal showed to be overall rare, short-distance dispersal strategies increased with urbanization at small scales, but declined when urbanization was quantified at large scales. We discuss the putative drivers behind these differences in natal dispersal and highlight its importance for urban evolution and ecology.